AB0909 RETENTION RATE OF APREMILAST AND RISK FACTORS FOR INADEQUATE RESPONSE IN PATIENTS WITH PSORIATIC ARTHRITIS: RESULTS FROM AN ITALIAN MONOCENTRIC COHORT
Authors: L. Moschetti, F. Crisafulli, F. Canova, F. Franceschini, L. Andreoli, M. Frassi
Journal: Annals of the Rheumatic Diseases (2022)

Background Apremilast (APR) is an oral PDE4 inhibitor approved for the treatment of Psoriatic Arthritis (PsA). Its effectiveness has been assessed in clinical trials 1,2 , but real-life data are still scarce. Objectives To evaluate the retention rate (RR) of APR in PsA patients and the risk factors associated to APR inadequate response. Methods Retrospective monocentric analysis of PsA patients (CASPAR criteria 2006) treated with APR between 2017 and 2021. Disease activity was evaluated at baseline (T0) and after 6 (T6), 12 (T12) and 24 (T24) months of therapy using DAPSA score. Data are expressed as median [IQR]. Results The cohort included 79 patients (41% males; age at PsA onset: 47 [37-58] years). PsA domains were: oligoarticular involvement (58%), enthesitis (42%), dactylitis (6%), axial involvement (13%), psoriasis (62%). Half patients presented dysmetabolic traits: 47% overweight/obesity, 34% arterial hypertension, 20% dyslipidemia. APR was prescribed mainly as first-line targeted therapy; in 42% APR was administered after the failure of ≥1 bDMARD. Contraindications to bDMARDs (47%) especially increased infectious risk (19/37) and current/previous malignancy (15/37), and mild PsA phenotype (27%) were the main reasons for APR choice. APR was discontinued in 61% after 4 [1-10] months because of inefficacy (25/48) or adverse events (AEs) (21/48; 81% gastrointestinal complaints). Patients who discontinued APR were compared with patients who continued APR (Table 1). Table 1. APR WITHDRAWAL n=48 APR CONTINUATION n=31 p value Females 28 (58) 19 (61) 0.79 Age at T0, years 51 [44-58] 57 [53-71] 0.03 PsA duration at T0, years 5 [2-11] 5 [0-12] 0.81 Oligoarticular involvement 24 (50) 20 (65) 0.21 Axial involvement 6 (13) 4 (13) 1.00 Enthesitis / dactylitis 26 (54) 11 (36) 0.10 DAPSA at T0 22 [16-28] 18 [13-26] 0.27 APR in monotherapy 26 (54) 23 (74) 0.07 bDMARDs naïve 24 (50) 22 (71) 0.07 Results are presented as median [IQR] or number (%). Continuous variables were compared with Mann-Whitney test; categorical variables were compared with Chi Squared/exact Fisher test. The RR of APR was 62% at T6, 51% at T12 and 38% at T24 (Figure 1 a ). Figure 1. a) Overall RR of APR b) RR of APR in bDMARDs naïve vs previously treated with bDMARDs patients (exclusion of withdrawals for intolerance). In patients continuing therapy, APR showed a good efficacy, with a significant reduction of DAPSA score observed at T6 (13 [9-19]), T12 (11 [4-18]) and T24 (8 [3-10]) as compared to T0 (21 [14-28]) (p&lt;0.01). An overall trend of reduction of the BMI (kg/m 2 ) was observed (T0: 25 [22-28], T6: 24 [21-27], T12: 23 [21-26]); in overweight patients the BMI decreased significantly (28 [26-31] at T0 vs 27 [26-29] at last evaluation; p&lt;0.01). Because of the high rate of discontinuations due to intolerance in the first months of therapy, we conducted a sub analysis: patients who continued APR (n=31) vs patients who discontinued it for inefficacy (n=25). A higher frequency of APR withdrawal was registered in younger patients (51 [47-57] vs 57 [53-71] years; p:0.01) previously treated with bDMARDs (71% vs 40%; p:0.02). Multivariate analysis confirmed these associations (OR [95% CI]: 0.1 [0.89-0.99], p:0.03 and 2.3 [1.70-59.17], p:0.01; respectively). The RR was higher in bDMARDs naïve patients compared with patients previously treated with bDMARDs (T6: 75% vs 67%, T12: 71% vs 63%, T24: 67% vs 34%; log-rank test= p:0.05) (Figure 1 b ). Conclusion This study confirms the safety and effectiveness of APR in a real-life scenario. We experienced a higher APR withdrawal rate for AEs (44%) in the first months of therapy, compared to registration studies in which APR was suspended in (8%). However, when tolerated, APR maintained efficacy over time, as demonstrated by progressive DAPSA reduction. The higher RR in bDMARDs naïve patients suggests the early use of APR. Moreover, the reduction of BMI could favor APR use in dysmetabolic patients. These data need to be confirmed in larger studies. References [1]Edwards CJ et al. Ann Rheum Dis. 2016. 1 Kavanaugh A et al. Arthritis Res Ther. 2019. Disclosure of Interests None declared